Airspace enlargement with airway cell apoptosis in klotho mice: A model of aging lung

Abstract

Homozygous mutant klotho (KL-/- ) mice exhibit various characteristics resembling those of human aging, including emphysema. However, age-related changes of lungs have not been fully elucidated. Here, we investigated the structural, functional, biochemical, and cell kinetic alterations of lungs in KL-/- mice at 2-12 weeks of age. Homogeneous airspace enlargement and decreased lung elastic recoil were observed in KL -/- mice with aging. The apoptotic cells in airway walls in KL -/- mice were approximately 6 times greater than those in wild-type (KL+/+) mice at 2 weeks of age. However, lipid peroxidation and elastase activity of lungs were not increased in KL-/- mice. Western blotting suggested that protein levels of epidermal growth factor (EGF) and phosphorylated extracellular signal-regulated kinase were decreased in KL -/- mice. These data suggest that significantly increased apoptosis of airway cells via inhibition of the EGF-dependent pathway may be involved in the development of the aging lungs in KL-/- mice. Copyright 2008 by The Gerontological Society of America.